Mechanisms of Adrenal Differentiation

肾上腺分化的机制

• 批准号: 8217213
• 负责人: GARY D. HAMMER
• 金额: $ 31.8万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2013-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217213
• 关键词: Activities of Daily Living; Adrenal Cortex; Adrenal Gland Diseases; Adrenal Glands; Cell Cycle; Cells; Cellular biology; Corticotropin; Data; Disease; Future; Gene Targeting; Genes; Genomics; Growth; Hormones; Laboratories; Maintenance; Malignant Neoplasms; Molecular; Organ failure; Pathway interactions; Population; Process; Proliferating; Property; Regulation; Role; SF1; Signal Pathway; Stem cells; System; Therapeutic; Undifferentiated; base; capsule; in vivo; mouse model; novel; programs; response; self-renewal; stem; stem cell niche; transcription factor

PROPOSAL ABSTRACT The long range objective of our laboratory is to understand the cellular and molecular mechanisms by which signaling pathways and downstream transcription factors coordinate the specification of adrenocortical cells within the adrenal gland. Our strategy for this proposal is to focus on the role of SF1 and the SF1 target gene Dax1 in the regulation of adrenocortical growth maintenance. Based on our preliminary data, we hypothesize that unique transcriptional programs in subcapsular undifferentiated progenitor cells serve to maintain the functional capacity of the adrenal cortex. Our specific aims are directed towards a systematic characterization of novel functions of SF1 critical to this process. We propose to determine the origin of the SF1 positive subcapsular cells (specific aim 1), define the role of Dax1 in the self-renewal and multipotent properties of these adrenocortical cells in vivo (specific aim 2) and determine the mechanisms by which SF1 is activated to initiate a unique proliferation-associated transcriptional profile in this subcapsular population (specific aim 3). The studies proposed here will provide the critical framework for understanding the role of SF1 in adrenocortical stem/progenitor cells in adrenal growth maintenance and lay the groundwork for future therapeutic efforts in diseases of adrenal growth including both hypoplasias and cancer.

提案摘要 我们实验室的远距离目标是了解细胞和分子机制 信号通路和下游转录因子协调肾上腺皮质细胞的规范 在肾上腺内。 我们对该提案的策略是专注于SF1和SF1靶基因DAX1在调节中的作用 肾上腺皮质增长维持。 基于我们的初步数据，我们假设在亚皮亚中，独特的转录程序 未分化的祖细胞可维持肾上腺皮质的功能能力。 我们的具体目标是针对SF1新功能的系统表征至关重要的 过程。我们建议确定SF1阳性亚囊细胞的起源（特定目标1），定义 DAX1在体内这些肾上腺皮质细胞的自我更新和多元特性中的作用（特定目标2） 并确定激活SF1以启动独特相关的机制 该亚囊中种群中的转录曲线（特定目的3）。 这里提出的研究将为理解SF1的作用提供关键框架 肾上腺生长维持中的肾上腺皮质干/祖细胞，并为将来奠定基础 肾上腺疾病疾病的治疗努力，包括促脑和癌症。